The study of the performance and properties of the physiology (including notably the cardiovascular system) of a living subject has proven useful for diagnosing and assessing any number of conditions or diseases within the subject. The performance of the cardiovascular system, particularly the heart, has characteristically been measured in terms of several pertinent parameters, such as pulse wave velocity, pulse transit time, stroke volume and cardiac output.
A key cardiovascular parameter (or physiological characteristic) is pulse wave velocity, i.e. the speed at which a pressure wave propagates throughout the arterial tree, or aortic pulse wave velocity, i.e. the speed at which a pressure wave propagates through the aorta or central arterial tree. As is well known in the art, pulse wave velocity measurements are often employed to evaluate the status of the cardiovascular system, particularly, the central arteries, e.g., as an index of large artery elasticity and stiffness. Pulse wave velocity measurements are also often employed to determine additional cardiovascular characteristics, such as stroke volume and cardiac output.
Arterial stiffness encompasses several properties, such as vascular distensibility, compliance and elastic modulus, and has been shown to be a good predictor of coronary heart disease and cardiovascular mortality. See, e.g., O'Rourke, et al., Am J Hypertens, vol. 15, pp. 426-444 (2002); Boutouyrie, et al., Hypertension, vol. 39, pp 10-15 (2002); Blacher, et al., Circulation, vol. 99, pp 2434-2439 (1999). In general, increased arterial stiffness can lead to increased systolic pressure, increased ventricular mass, and decreased diastolic coronary perfusion. Increased arterial stiffness has also been associated with reduced flow volume in the lower-extremity arteries. See e.g., Suzuki, et al., Diabetes Care, vol. 24, pp 2107-2114 (2001).
Various conventional methods, techniques and associated algorithms have been employed to determine pulse wave velocity. Illustrative are the methods described below.
Referring first to FIG. 1, there is shown a method for determining pulse wave velocity, which is commonly referred to as the “Frank” method. According to the “Frank” method, two pulse wave sensors (designated “P1” and “P2”) are used to detect a pulse wave of the carotid artery and a pulse wave of the femoral artery. Distances “a” and “b+c” between the aortic valve region and respective pulse wave detection points are measured.
Referring to FIG. 2, the carotid artery pulse wave, which is obtained by the carotid artery pulse wave sensor (“P1”), exhibits a waveform indicated by “a”. The femoral artery pulse wave, which is obtained by the femoral artery pulse wave sensor (“P2”), exhibits a waveform indicated by “b”.
Predetermined rising times of the pulse waves, each of which correspond to a time when a level value reaches ⅕ of a peak value (designated “RT1” and “RT2”), are compared with each other to obtain a time difference between, i.e. time T. The pulse wave velocity (PWV) is then determined using a basic physics algorithm, i.e. velocity equals distance over time.
Referring now to FIGS. 3 and 4, there is shown a further method for determining pulse wave velocity, which is commonly referred to as a PWV original method. As illustrated in FIG. 3, according to this method, sensors are located in positions proximate the carotid and femoral arteries (designated “P3” and “P4”, respectively) to detect pulse waves therein. In addition, a heart sound sensor (designated “HSS”) is located proximate the aortic valve region. A straight distance “D” between the aortic valve region and the femoral artery pulse wave sensor (“P4”) is measured. Distance “D” is then multiplied by 1.3, i.e. a correction factor to provide actual arterial path.
There are several drawbacks and disadvantages associated with the Frank and PWV original methods. A major drawback is that it is generally more difficult to capture and maintain an accurate pulse wave signal via the noted methods.
Further methods and associated algorithms for determining pulse wave velocity are disclosed in McDonald, et al., “Left Ventricular Output Derived from the Time-Derivative and Phase Velocities of the Aortic Pressure Wave”, Medical and Biological Engineering, vol. 11, pp. 678-690 (November 1973); D. A. McDonald, “The Relation of Pulsatile Pressure to Flow in Arteries”, J. Physiology, vol. 127, pp. 533-552 (1955) and G. O. Barnett, “The Technique of Estimating Instantaneous Aortic Blood Velocity in Man from the Pressure Gradient”, American Heart Journal, vol. 62, No. 3, pp. 359-366 (September 1961), and U.S. patent application Ser. No. 11/344,106 (Pub. No. 2006/0173366A1); Ser. No. 11/418,787 (Pub. No. 2006/0281668 A1); Ser. No. 10/591,742 (Pub. No. 2007/0197924); Ser. No. 11/453,848 (Pub. No. 2007/0004985) and Ser. No. 11/475,917 (Pub. No. 2007/0016085).
Although the methods disclosed in the noted references provide an effective means of determining pulse wave velocity, the methods are susceptible to significant error by virtue of the fact that the determinations of pulse transit time, which is a primary variable in pulse wave velocity equations and algorithms, fail to adequately account for the pre-ejection period (“PEP”).
As discussed in detail herein, the error resulting from failing to account for PEP in a pulse transit time determination, which is carried into a pulse wave velocity determination, can vary, unpredictably in the range of 10-25% or more.
It would therefore be desirable to provide an improved method for accurately determining the pre-ejection period of a subject.
It would also be desirable to provide an improved method for determining pulse wave velocity that provides an accurate measure of pulse wave velocity by effectively accounting for the pre-ejection period.
As is well known in the art, there is diagnostic value and clinical utility for interventional therapy in either or both parameters, i.e. pre-ejection period and pulse wave velocity, as pre-ejection period is indicative mostly of the condition of the myocardium, whereas pulse wave velocity is mostly an indicator of the condition of the vasculature.
It is therefore an object of the present invention to provide improved methods for determining the pre-ejection period and pulse wave velocity that substantially reduce or eliminate the disadvantages and drawbacks associated with conventional methods and algorithms for determining the pre-ejection period and pulse wave velocity.
It is another object of the present invention to provide a method and algorithm for accurately determining the pre-ejection period.
It is another object of the present invention to provide a method and algorithm for determining pulse wave velocity that provides an accurate measure of pulse wave velocity by effectively accounting for the pre-ejection period.
It is another object of the present invention to provide a method for accurately determining cardiac output.
It is another object of the present invention to provide an improved method for assessing the status of the cardiovascular system.